crossing96/oncoscreening huggingface dataset:
Performance of an artificial intelligence algorithm for reporting urine cytopathology.	BACKGROUND: Unlike Papanicolaou tests, there are no commercially available computer-assisted automated screening systems for urine specimens. Despite The Paris System for Reporting Urinary Cytology, there still is poor interobserver agreement with urine cytology and many cases in which a definitive diagnosis cannot be made. In the current study, the authors have reported on the development of an image algorithm that applies computational methods to digitized liquid-based urine cytology slides. METHODS: A total of 2405 archival ThinPrep glass slides, including voided and instrumented urine cytology cases, were digitized. A deep learning computational pipeline with multiple tiers of convolutional neural network models was developed for processing whole slide images (WSIs) and predicting diagnoses. The algorithm was validated using a separate test data set comprised of consecutive cases encountered in routine clinical practice. RESULTS: There were 1.9 million urothelial cells analyzed. An average of 5400 urothelial cells were identified in each WSI. The algorithm achieved an area under the curve of 0.88 (95% CI, 0.83-0.93). Using the optimal operating point, the algorithm's sensitivity was 79.5% (95% CI, 64.7%-90.2%) and the specificity was 84.5% (95% CI, 81.6%-87.1%) for high-grade urothelial carcinoma. CONCLUSIONS: The authors successfully developed a computational algorithm capable of accurately analyzing WSIs of urine cytology cases. Compared with prior studies, this effort used a much larger data set, exploited whole slide-level and not just cell-level features, and used a cell gallery to display the algorithm's output for easy end-user review. This algorithm provides computer-assisted interpretation of urine cytology cases, akin to the machine learning technology currently used for automated Papanicolaou test screening.	bladder
The Cost to Medicare of Bladder Cancer Care.	BACKGROUND: Bladder cancer care is costly, including cost to Medicare, but the medical cost associated with bladder cancer patients relative to identical persons without bladder cancer is unknown. OBJECTIVE: To determine incremental bladder cancer cost to Medicare and the impact of diagnosis stage and bladder cancer survival on cost. DESIGN, SETTING, AND PARTICIPANTS: A case-control study was conducted using 1998-2013 Surveillance, Epidemiology and End Results-Medicare data. Controls were propensity score matched for diagnosis year, age, gender, race, and 31 Elixhauser Comorbidity Index values. Three incident cohorts, 1998 (n=3136), 2003 (n=7000), and 2008 (n=7002), were compared. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival following diagnosis and Medicare payments (in 2018 dollars) were tabulated, and compared between cases and controls. RESULTS AND LIMITATIONS: From 1998 to 2008, bladder cancer patients became older and had more comorbidities at diagnosis, although no stage migration or change in survival occurred. Incremental costs (above those associated with controls) were highest during the 1st year after diagnosis and were higher for distant ($47533) than for regional ($42403) or localized ($14304) cancer. Bladder cancer survival was highly stage dependent. After an initial spike in costs lasting 1-2yrs, monthly costs dropped in survivors but remained higher than for controls. Long-term survivors in the full sample accrued cumulative Medicare costs of $172426 over 16yrs-46% higher than for controls. Limitations include omission of indirect costs and reliance on traditional Medicare. CONCLUSIONS: While a bladder cancer diagnosis incurs initial high Medicare cost, particularly in patients with advanced cancers, the cumulative costs of bladder cancer in long-term survivors are higher still. Bladder cancer prevention saves Medicare money. However, while early detection, better therapies, and life extension of bladder cancer patients are worthwhile goals, they come at the cost of higher Medicare outlays. PATIENT SUMMARY: The lifetime cost of bladder cancer, reflecting surveillance, treatment, and management of complications, is substantial. Since care is ongoing, cost increases with the length of life after diagnosis as well as the severity of initial diagnosis.	bladder
Combined Next-generation Sequencing and Flow Cytometry Analysis for an Anti-PD-L1 Partial Responder over Time: An Exploration of Mechanisms of PD-L1 Activity and Resistance in Bladder Cancer.	Anti-PD-L1/PD-1 immunotherapy has improved survival for certain patients with metastatic urothelial carcinoma. However, the mechanisms of resistance to these agents have not been fully elucidated. We report the first combined analysis using RNA sequencing, whole-exome sequencing (WES), and flow cytometry of multiple tumor specimens over a 5-yr period for a patient undergoing anti-PD-L1 therapy. Initial sensitivity to anti-PD-L1 immunotherapy was associated with conversion to a basal molecular subtype and a rising tumor mutational burden. We found that as the tumor became more resistant to anti-PD-L1, the proportion of regulatory T cells and CD8(+) T cells expressing alternative immune checkpoints including CTLA-4, TIM-3, and LAG-3 increased. This suggests that alternative immune checkpoint upregulation may be one form of anti-PD-L1 resistance in urothelial carcinoma. These data support the concept of combined immune checkpoint blockade for urothelial carcinoma, a concept that is being evaluated in prospective clinical trials. PATIENT SUMMARY: In this study we characterized how a patient with metastatic urothelial cancer became resistant to anti-PD-L1 immunotherapy. By tracking changes in protein and gene expression over time, we found that as urothelial carcinoma becomes resistant to PD-L1 blockade, additional immune checkpoints may be upregulated. These data support the concept of combined checkpoint blockade for urothelial carcinoma.	bladder
Discerning Patterns and Quality of Neoadjuvant Chemotherapy Use Among Patients with Muscle-invasive Bladder Cancer.	BACKGROUND: Neoadjuvant chemotherapy is underutilized in bladder cancer patients who undergo radical cystectomy. However, the quality of regimens used in this setting remains largely unknown. OBJECTIVE: To determine utilization treatment patterns and survival outcomes according to regimens administered. DESIGN, SETTING, AND PATIENTS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients diagnosed with clinical stage TII-IV bladder cancer from January 1, 2001 to December 31, 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Temporal trends were assessed using the Cochran-Armitage test. Multivariable logistic regression models were used to identify predictors for neoadjuvant chemotherapy use. Cox proportional hazards models were used to compare overall survival according to regimens administered. RESULTS AND LIMITATIONS: Of 2738 patients treated with radical cystectomy, 344 (12.6%) received neoadjuvant chemotherapy. The agents most commonly used were gemcitabine (72.3%), cisplatin (55.2%), and carboplatin (31.1%). The regimens most commonly used were gemcitabine-cisplatin (45.3%), gemcitabine-carboplatin (24.1%), and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC; 6.7%). Use of neoadjuvant chemotherapy more than tripled during the study period, from 5.7% in 2001 to 17.3% in 2011 (p<0.001). The quality of the regimen administered impacted survival outcomes, as M-VAC use was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer (hazard ratio 0.24, 95% confidence interval 0.07-0.86; p=0.030]. Limitations include the limited ability of retrospective analysis to control for selection bias. CONCLUSIONS: Neoadjuvant chemotherapy was underused, and the quality of neoadjuvant chemotherapy regimens administered for bladder cancer was inconsistent with guideline recommendations. These findings are important when interpreting population-based data on the use of chemotherapy and extrapolating survival outcomes. PATIENT SUMMARY: In a large population-based study, 12.6% of patients undergoing radical cystectomy for bladder cancer received neoadjuvant chemotherapy, half of whom received guideline-recommended regimens. The quality of the regimen impacted survival outcomes, as use of cisplatin-based chemotherapy was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer. However, <1% of radical cystectomy patients received this regimen.	bladder
Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers.	BACKGROUND: Bladder cancer (BC) is highly immunogenic. Bacillus Calmette-Guérin (BCG) immunotherapy offers the best results in non-muscle-invasive BC (NMIBC). Natural killer cells (NKcs) play decisive roles in BCG-mediated immune response and in general cancer immune-surveillance. OBJECTIVE: To analyze killer-cell immunoglobulin-like receptors (KIRs), their human leukocyte antigen class-I (HLA-I) ligands, and the expression of DNAX Accessory Molecule-1 (DNAM-1/CD226) on peripheral blood (PB) NKcs, to identify useful predictive biomarkers in BC. DESIGN, SETTING, AND PARTICIPANTS: KIR/HLA-ligand genotypes were compared between 132 BC, 201 other solid cancers, 164 plasma cell disorders, and 615 healthy Caucasoid controls. CD226 expression was evaluated by flow cytometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: KIR/HLA-I interactions and CD226 expression on NKcs (CD226(high) or CD226(low)) were compared across study groups, cancer stages, treatments, and progression-free and overall survival of patients, using chi-square, analysis of variance/post hoc, Kaplan-Meier/log-rank, and regression analyses. RESULTS AND LIMITATIONS: Three immunological risk groups were identified: low risk (KIR2DL1(-)L2(+)L3(-)/C1C1(-) and KIR2DL1(+)L2(+)L3(+)/C1C1(+)), intermediate risk (rest), and high risk (KIR2DL5(+)/HLA-C*16(+) and KIR2DL1(+)L2(+)L3(-)), which displayed different 10-yr progression-free rates (83.3%, 48.6%, and 0%, respectively; p<0.001) and survival rates (83.3%, 54.3%, and 6.2%, respectively; p<0.001) for muscle-invasive T2/T4, and 10-yr progression-free rates (100%, 81.6%, and 50%, respectively; p<0.05) for NMIBC-T1 treated with BCG. Immunological risk stratification had an independent prognostic value to just histological staging for survival (hazard ratio=2.93, p<0.00001, Harrell C-statistic=0.779). CD226 expression on PB NKcs improved immunological stratification in intermediate-risk T1-T4 BC patients, with survival rates of 94.1% and 66.7% for CD226(high) and CD226(low) (p<0.05), respectively. CONCLUSIONS: Immunological risk stratification will complement BC histopathology to improve risk stratification and guide the selection of personalized treatments. Understanding of the molecular mechanisms of NKc tumor immune surveillance will enable the development of future NKc-based therapies. PATIENT SUMMARY: This work describes a peripheral blood test that aids in our understanding of the immune defense mechanisms against bladder cancer, is useful for classifying patient risk, and will guide personalized treatments.	bladder
Chemoablation with Intensive Intravesical Mitomycin C Treatment: A New Approach for Non-muscle-invasive Bladder Cancer.	BACKGROUND: Mitomycin C (MMC) is widely used, but the optimal dose and schedule have not been established. OBJECTIVE: To evaluate the ablative power and patient safety of a short-term intensive schedule of intravesical MMC in patients with recurrent non-muscle-invasive bladder cancer (NMIBC). DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, single-center, nonrandomized study that compared 47 patients (group 1) with a history of low- to intermediate-risk NMIBC with long free-recurrence intervals, recurrence of ≤1cm in maximum diameter, and negative cytology to 47 consecutive patients with the same baseline characteristics (group 2). INTERVENTION: Intravesical MMC three times per week for 2 wk for group 1. Transurethral resection of bladder tumor (TUR-BT) and early instillation and a weekly schedule of intravesical MMC for group 2. All cancer-free patients underwent monthly MMC maintenance. Follow-up included bladder mapping, voiding and washing urinary cytology, TUR of suspected area, TUR of previous tumor location, and ultrasound or computed tomography/magnetic resonance imaging. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: We used χ(2) and Student's t test for comparison of categorical and continuous variables, respectively. Kaplan-Meier curves were plotted to estimate cancer-free survival. The significance level was set to p<0.05. RESULTS AND LIMITATIONS: The complete response rate at 39 mo was 61.7% in group 1 and 70.2% in group 2 (p=0.38). Kaplan-Mayer analysis revealed no difference in cancer-free survival rates overall (log-rank <3.84), according to tumor size in each group (log-rank <3.84), or between the groups (log-rank <7.82). No cases of systemic toxicity were observed. Local toxicities did not differ between the groups (p=0.32) and resolved on treatment of symptoms, and no patient discontinued their treatment. Limitations include the small number of patients, selection bias because of the single tertiary center, and short follow-up. CONCLUSIONS: The proposed MMC schedule had good ablative power that can be explained by better concordance between the scheduled timing and the tumor cell duplication rate. The short-term intensive schedule could be considered as a therapeutic strategy to replace TUR-BT in selected NMIBC patients. PATIENT SUMMARY: We report our experience of a tailored intravesical therapy schedule for bladder cancer. This schedule could be considered a therapeutic strategy to replace surgery for selected patients.	bladder
N(6)-methyladenosine modification of ITGA6 mRNA promotes the development and progression of bladder cancer.	BACKGROUND: Accumulating evidence has revealed the critical roles of N(6)-methyladenosine (m(6)A) modification of mRNA in various cancers. However, the biological function and regulation of m(6)A in bladder cancer (BC) are not yet fully understood. METHODS: We performed cell phenotype analysis and established in vivo mouse xenograft models to assess the effects of m(6)A-modified ITGA6 on BC growth and progression. Methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation and luciferase reporter and mutagenesis assays were used to define the mechanism of m(6)A-modified ITGA6. Immunohistochemical analysis was performed to assess the correlation between METTL3 and ITGA6 expression in bladder cancer patients. FINDINGS: We show that the m(6)A writer METTL3 and eraser ALKBH5 altered cell adhesion by regulating ITGA6 expression in bladder cancer cells. Moreover, upregulation of ITGA6 is correlated with the increase in METTL3 expression in human BC tissues, and higher expression of ITGA6 in patients indicates a lower survival rate. Mechanistically, m(6)A is highly enriched within the ITGA6 transcripts, and increased m(6)A methylations of the ITGA6 mRNA 3'UTR promotes the translation of ITGA6 mRNA via binding of the m(6)A readers YTHDF1 and YTHDF3. Inhibition of ITGA6 results in decreased growth and progression of bladder cancer cells in vitro and in vivo. Furthermore, overexpression of ITGA6 in METTL3-depleted cells partially restores the BC adhesion, migration and invasion phenotypes. INTERPRETATION: Our results demonstrate an oncogenic role of m(6)A-modified ITGA6 and show its regulatory mechanisms in BC development and progression, thus identifying a potential therapeutic target for BC. FUND: This work was supported by National Natural Science Foundation of China (81772699, 81472999).	bladder
Multicenter Analysis of Postoperative Complications in Octogenarians After Radical Cystectomy and Ureterocutaneostomy: The Role of the Frailty Index.	BACKGROUND: The purpose of this study was to assess patient frailty as a risk factor for radical cystectomy (RC) complications. MATERIALS AND METHODS: We performed an analysis of prospectively collected data of consecutive patients 80 years of age or older who underwent RC and ureterocutaneostomy in 6 primary care European urology centers. Frailty was measured using a simplified frailty index (sFI) with a 5-item score including: (1) diabetes mellitus; (2) functional status; (3) chronic obstructive pulmonary disease; (4) congestive cardiac failure; and (5) hypertension, with a maximum 5-item score meaning high level of frailty. Within 90 days surgical complications were scored according to the Clavien Classification System (CCS). sFI ≥3 was considered as poor frailty status. Clinical and pathological variables were analyzed as predictors of severe complications (CCS ≥3). RESULTS: One hundred seventeen patients were enrolled. Most patients reported an sFI score of 2 and 3, respectively, 31/117 (26.5%) and 45/117 patients (38.5%). CCS ≥3 occurred in 17/117 patients (14.5%). Patients with sFI ≥3 were significantly older than patients with sFI <3 (median age, 85 years [interquartile range (IQR), 82-86] versus 82 years [IQR, 80-84]; P = .001). Most CCS ≥3 scores occurred in patients with sFI ≥3: 13 (11.1%) versus 4 (3.4%; P = .02). No significative differences were detected in terms of length of hospital stay, pathological stage, and postoperative bowel canalization when related to sFI. sFI ≥3 was an independent risk factor of CCS ≥3 in univariate and multivariate analysis (respectively, odds ratio [OR], 3.81 [95% confidence interval (CI), 1.16-12.5; P = .02] and OR, 3.1 [95% CI, 0.7-13.7; P = .01]). Body mass index, age, American Society of Anesthesiologists score ≥3, and pathological stage were not related to CCS ≥3. CONCLUSION: RC appears feasible in elderly patients with an sFI <3. In cases of sFI ≥3, this choice should be carefully valued, discussed, and possibly avoided because of a higher risk of complications.	bladder
[Follow-up surveillance of muscle-invasive urinary bladder cancer after curative treatment].	Follow-up care of patients with muscle-invasive bladder cancer is subdivided into oncological and functional surveillance. More than 80% of local relapses and distant metastases occur within the first 2 years. Recurrences in the remnant urothelium also occur several years after radical cystectomy. Urinary cytology and a computed tomography (CT) scan of the abdomen and thorax including a urography phase are the standard diagnostics for tumor follow-up. There is no clear evidence for a survival benefit for the detection of asymptomatic vs. symptomatic recurrences. After partial cystectomy or trimodal treatment, there is no established follow-up schedule; however, the relatively high incidence of intravesical recurrences should be considered as there are curative treatment approaches including salvage cystectomy. Functional surveillance, which should be carried out lifelong, encompasses prevention and diagnostics of metabolic complications, urethral/ureteral strictures, problems with the urinary stoma, urinary incontinence, sexual dysfunction and urinary tract infections.	bladder
Scented Candles as an Unrecognized Factor that Increases the Risk of Bladder Cancer; Is There Enough Evidence to Raise a Red Flag?	The causes of bladder cancer are not yet fully uncovered, however the research has identified a number of factors that may increase the risk of developing this cancer. The chemical carcinogenesis of bladder cancer due to chronic exposure to aromatic hydrocarbons has been well-established. The identification of this correlation led to an improvement of safety measures in chemical industry and a gradual decrease of bladder cancer cases among workers. Nevertheless, in the majority of bladder cancer cases, the specific cause of the disease still can't be specified. It makes the question of unrecognized factors associated with bladder cancer development even more relevant. Taking under consideration known chemical carcinogenesis of bladder cancer, this minireview takes under investigation the possible link between using scented candles and a risk of bladder cancer development. Burning scented candles contain many of the substances that are associated with a bladder cancer. Furthermore the scented candles are not only very popular but also widely available on the market, with limited quality regulations and unspecified raw materials determining a spectrum of potentially dangerous substances emitted during burning.	bladder
Involvement of Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and the PI3K/AKT/mTOR Pathway in Nobiletin-Induced Apoptosis of Human Bladder Cancer Cells.	Nobiletin (NOB) is a polymethoxylated flavonoid isolated from citrus fruit peel that has been shown to possess anti-tumor, antithrombotic, antifungal, anti-inflammatory and anti-atherosclerotic activities. The main purpose of this study was to explore the potential of using NOB to induce apoptosis in human bladder cancer cells and study the underlying mechanism. Using an MTT assay, agarose gel electrophoresis, a wound-healing assay, flow cytometry, and western blot analysis, this study investigated the signaling pathways involved in NOB-induced apoptosis in BFTC human bladder cancer cells. Our results showed that NOB at concentrations of 60, 80, and 100 μM inhibited cell growth by 42%, 62%, and 80%, respectively. Cells treated with 60 μM NOB demonstrated increased DNA fragmentation, and flow cytometry analysis confirmed that the treatment caused late apoptotic cell death. Western blot analysis showed that mitochondrial dysfunction occurred in NOB-treated BFTC cells, leading to cytochrome C release into cytosol, activation of pro-apoptotic proteins (caspase-3, caspase-9, Bad, and Bax), and inhibition of anti-apoptotic proteins (Mcl-1, Bcl-xl, and Bcl-2). NOB-induced apoptosis was also mediated by regulating endoplasmic reticulum stress via the PERK/elF2α/ATF4/CHOP pathway, and downregulating the PI3K/AKT/mTOR pathway. Our results suggested that the cytotoxic and apoptotic effects of NOB on bladder cancer cells are associated with endoplasmic reticulum stress and mitochondrial dysfunction.	bladder
Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma.	PURPOSE/OBJECTIVE(S): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. MATERIALS/METHODS: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. RESULTS: The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). CONCLUSIONS: PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.	bladder